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Ji Cheng Zhang, Jin Hua Wang, Jia Lin, Guo Ming Su, Yi Lin Shen, Qi Wei Guo, Jia Jing Cai, Jun Yi Liu, Ke Xin Jia, Ding Zhi Fang Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ding Zhi Fang, Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, People’s Republic of China, Email dzfang@scu.edu.cnAim: To explore anthropometric, metabolic and dietary factors associated with and their interplays with the Val66Met polymorphism at brain-derived neurotrophic factor (BDNF) gene (Bdnf) on serum BDNF levels in adolescents.Methods: Serum BDNF levels were quantified using an enzyme-linked immunosorbent assay in 644 high school students (278 males/366 females). A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for Bdnf Val66Met genotyping followed by verification using DNA sequencing. Serum levels of metabolic characteristics were assayed by routine methods. The intake of macro and micronutrients was collected by a three-day food record.Results: Serum BDNF levels were found to be significantly different in the subjects with different genotypes of Bdnf Val66Met (Val/Val homozygotes, 60.05 ± 28.07 ng/mL vs Val/Met heterozygotes, 56.37 ± 29.34 ng/mL vs Met/Met homozygotes, 51.32 ± 24.54 ng/mL, p = 0.022). Among the 36 tested variables, waist–hip ratio (WHR) (β = − 0.163, p < 0.001), iodine intake (β = 0.132, p = 0.001), heart rate (β = 0.108, p = 0.005), high-density lipoprotein cholesterol (HDL-C) (β = 0.098, p = 0.011) and dietary fiber intake (β = 0.082, p = 0.084) were the predictor of serum BDNF levels, while SBP (β = 0.097, p = 0.013) and WHR (β = 0.091, p = 0.021) were related with Bdnf Val66Met. Moreover, WHR was observed to play a partial mediating role in the relationship between Bdnf Val66Met and serum BDNF levels (95% CI [− 1.161, − 0.087]) and contribute 13.05% of its total effect on serum BDNF levels.Conclusion: There are interplays between WHR and Bdnf Val66Met on serum BDNF levels, which may be among the explanations for the previous heterogeneous reports and provide novel insights into the regulation of serum BDNF levels.Keywords: serum, brain-derived neurotrophic factor, Val66Met, waist–hip ratio, mediator, adolescent

Shun Yu Sun,1 Wei Yi Yang,2 Zhuo Tan,2 Xing Yu Zhang,1 Yi Lin Shen,1 Qi Wei Guo,1 Guo Ming Su,1 Xu Chen,1 Jia Lin,1 Ding Zhi Fang1 1Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Preventive Medicine, West China School of Public health, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Ding Zhi FangDepartment of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, People’s Republic of China, Tel +86 28 85503410, Fax +86 28 85503204, Email dzfang@scu.edu.cnPurpose: To investigate serum levels of free fatty acids (FFAs) and their associations with routine serum lipids in diet-induced obese mice, which have been scantily reported before.Methods: Male C57BL/6 J mice were fed high-fat diets for 12 weeks to induce obesity. Levels of serum FFAs were measured by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.Results: Obese mice had higher serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), but lower triglycerides (TG) than control mice. A total of 30 FFAs were found, and 3 saturated fatty acids (SFAs), all 8 monounsaturated fatty acids (MUFAs) and 7 polyunsaturated fatty acids (PUFAs) decreased in obese mice, but one SFA (C4:0) increased. Differences in the relative levels of individual FFAs to total FFAs, SFAs, MUFAs or PUFAs between obese and control mice were different from each other and from those evaluated by concrete levels except C4:0, C16:1, C19:1 and C18:4. Only the concrete levels of C4:0, C22:3 and C18:4 were associated with routine serum lipids, including C22:3 negatively with TG in control mice, and C4:0 and C18:4 positively with LDL-C in obese mice, although the relative levels of C4:0 to total MUFAs negatively with TC, and C23:3 to total SFAs or MUFAs negatively with TG in control mice. Different relative levels of the remaining FFAs were differently associated with different routine serum lipids in obese and/or control mice.Conclusion: Obesity may influence serum FFAs profiles. The relationship of individual FFAs and their relative levels to other FFAs with routine serum lipids in obese and control mice suggests that individual FFAs may interact with others and obesity on levels of routine serum lipids. Once confirmed, the interactions may be novel perspectives when fatty acids are used to improve hyperlipidemia in the subjects with obesity.Keywords: free fatty acid, obesity, triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein

Yun-Liang Shen,1,* Si-Yu Long,2,* Wen-Ming Kong,1 Li-Mei Wu,1 Li-Juan Fei,1 Qiang Yao,1 Hong-Sheng Wang2 1Department of Leprosy Control, Zhejiang Provincial Institute of Dermatology, Huzhou, People’s Republic of China; 2Laboratory of Leprosy and Other Mycobacterial Infections, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Sheng WangLaboratory of Leprosy and Other Mycobacterial Infections, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, St 12 Jiangwangmiao, Nanjing, Jiangsu 210042, People’s Republic of ChinaEmail whs33@vip.sina.comQiang YaoDepartment of Leprosy Control, Zhejiang Provincial Institute of Dermatology, St 61, Wuyuan, Huzhou, Zhejiang 313200, People’s Republic of ChinaEmail 7793908@qq.comPurpose: Genome-wide association studies (GWAS) have identified multiple genetic variants associated with leprosy. To investigate the single and combined associations between single-nucleotide polymorphisms (SNPs) and the development of leprosy, we therefore performed generalized multi-analytical (GMDR) analysis in Chinese leprosy household contacts and constructed a risk prediction model.Patients and Methods: This case–control study included 229 leprosy cases and 233 healthy household contacts in Zhejiang province, China. Participants were genotyped for 17 polymorphisms selected from GWAS. The Pearson χ2 test, logistic regression and GMDR analysis were performed to investigate gene–gene interactions and construct a risk prediction model for leprosy.Results: The genotype and the allele distributions of rs142179458, rs2275606, rs663743 and rs73058713 were significantly different between patients and controls. rs2275606, rs6478108, rs663743 and rs73058713 showed an association after adjusting for sex and age in the logistic regression. A five-way interaction model consisting of rs2058660, rs2275606, rs4720118, rs6478108 and rs780668 was chosen as the optimal model for determining leprosy susceptibility. The model classified 237 (51.3%) into the low-risk group and 225 (48.7%) individuals into the high-risk group. The area under the curve (AUC) of this model was 0.757 (95% CI: 0.712– 0.803), and the odds ratio for leprosy between the high- and low-risk groups was 9.733 (95% CI: 6.384– 14.960; P< 0.001). The sensitivity and specificity of the model were observed to be 74.7% and 76.8%, respectively.Conclusion: Our results suggest that rs2058660, rs2275606, rs4720118, rs6478108 and rs780668, five SNPs with a significant sole effect on leprosy, interact to confer a higher risk for the disease in leprosy household contacts (HHCs).Keywords: leprosy, gene–gene interactions, generalized multi-analytical, risk stratification

Munirah Alsaleh,1 Thomas A Barbera,1 Helen L Reeves,2 Matthew E Cramp,3 Stephen Ryder,4,5 Hani Gabra,1,6 Kathryn Nash,7 Yi-Liang Shen,1,8 Elaine Holmes,1 Roger Williams,9 Simon D Taylor-Robinson11Division of Surgery and Cancer, Imperial College London, London; 2Northern Institute for Cancer Research, Medical School, University of Newcastle, Newcastle upon Tyne, UK; 3Liver Unit, Derriford Hospital, Plymouth, Devon , UK; 4Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK; 5NIHR Biomedical Research Unit, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, Nottingham, UK; 6Early Clinical Development, IMED Biotech Unit, AstraZeneca, Cambridge, UK; 7Liver Unit, Southampton General Hospital, Southampton, Hampshire, UK; 8Department of Radiation Oncology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; 9Institute of Hepatology, UKBackground: Outside South-East Asia, most cases of cholangiocarcinoma (CCA) have an obscure etiology. There is often diagnostic uncertainty. Metabolomics using ultraperformance liquid chromatography mass spectrometry (UPLC-MS) offers the portent to distinguish disease-specific metabolic signatures. We aimed to define such a urinary metabolic signature in a patient cohort with sporadic CCA and investigate whether there were characteristic differences from those in patients with hepatocellular carcinoma (HCC), metastatic secondary liver cancer, pancreatic cancer and ovarian cancer (OCA).Methods: Spot urine specimens were obtained from 211 subjects in seven participating centers across the UK. Samples were collected from healthy controls and from patients with benign hepatic disease (gallstone, biliary strictures, sphincter of Oddi dysfunction and viral hepatitis) and patients with malignant conditions (HCC, pancreatic cancer, OCA and metastatic cancer in the liver). The spectral metabolite profiles were generated using a UPLC-MS detector and data were analyzed using multivariate and univariate statistical analyses.Results: The greatest class differences were seen between the metabolic profiles of disease-free controls compared to individuals with CCA with altered acylcarnitine, bile acid and purine levels. Individuals with benign strictures showed comparable urine profiles to patients with malignant bile duct lesions. The metabolic signatures of patients with bile duct tumors were distinguishable from patients with hepatocellular and ovarian tumors, but no difference was observed between CCA cases and patients with pancreatic cancer or hepatic secondary metastases.Conclusion: CCA causes subtle but detectable changes in the urine metabolic profiles. The findings point toward potential applications of metabonomics in early tumor detection. However, it is key to utilize both global and targeted metabonomics in a larger cohort for in-depth characterization of the urine metabolome in hepato-pancreato-biliary disease.Keywords: cholangiocarcinoma, metabolomics, diagnostic biomarkers

This study was conducted to investigate the differences in chemical composition between red (RGBs) and yellow ginseng berries (YGBs) and their whitening and anti-aging skincare effects. The differences in the chemical composition between RGB and YGB were analyzed by ultra-high-performance liquid chromatography tandem quadrupole electrostatic field orbit trap mass spectrometry (UHPLC-Q-Exactive-MS/MS) combined with multivariate statistics. An aging model was established using UVB radiation induction, and the whitening and anti-aging effects of the two ginseng berries were verified in vitro and in vivo using cell biology (HaCaT and B16-F10 cells) and zebrafish model organisms. A total of 31 differential compounds, including saponins, flavonoids, phenolic acids, and other chemical constituents, were identified between the two groups. Superoxide dismutase (SOD) activity was more significantly increased ( p < 0.05) and malondialdehyde (MDA) content was more significantly decreased ( p < 0.01) in RGB more than YGB induced by UVB ultraviolet radiation. In terms of whitening effects, YGB was more effective in inhibiting the melanin content of B16-F10 cells ( p < 0.01). The results of zebrafish experiments were consistent with those of in vitro experiments and cell biology experiments. The DCFH fluorescence staining results revealed that both ginseng berries were able to significantly reduce the level of reactive oxygen species (ROS) in zebrafish ( p < 0.01). Comparison of chemical composition and skin care activities based on RGB and YGB can provide a theoretical basis for the deep development and utilization of ginseng berry resources.

Two new mushroom species from Southwest China, Pholiotacylindrospora and P.subterrestris , are described in this study. Pholiotacylindrospora is characterized by its dry pileus with slightly recurved and triangular scales, cylindrical basidiospores, and two types of pleurocystidia-leptocystidia and chrysocystidia-as well as its growth on soil. Pholiotasubterrestris is identified by a brownish-orange pileus with numerous brown fibrillose scales; pale brown lamellae with even edges; a stipe covered with recurved fibrillose scales; elliptical spores with a distinct but small germ pore; and pleurocystidia containing typical amorphous refractive inclusions of chrysocystidia. Both species are described and illustrated, and a phylogenetic analysis of a multigene dataset (ITS + 28S) is presented. Morphological and phylogenetic analyses confirm that P.cylindrospora and P.subterrestris are distinct from the other Pholiota species, and both belong to the subgenus Pholiota. A key to the species of subgenus Pholiota from China is provided., Competing Interests: The authors have declared that no competing interests exist., (Jia-hui Huang, Chun-yu Lei, Ya-lun Shen, En-jing Tian.)

Aims and Objectives: This study aimed to investigate the effectiveness of applying a multiphase optimization strategy (MOST) to enhance recovery after surgery (ERAS) protocols within the nursing management of children undergoing day surgery for snoring disease., Background: While MOST has been applied to behavioral intervention research in smoking cessation, AIDS management, and weight loss by international scholars, its application in constructing nursing intervention projects remains relatively unexplored., Design: Using convenience sampling, randomised controlled trial., Methods: A convenience sampling method was employed. The study recruited 200 preschool children diagnosed with snoring who underwent day surgery at a specific hospital between January 2023 and January 2024. The participants were divided into two groups: a control group receiving standard nursing care and an experimental group receiving MOST-guided, integrated high-quality nursing plans specifically designed for children with snoring undergoing day surgery, adhering to established ERAS guidelines., Results: Children in the experimental group exhibited significantly lower anxiety levels compared to the control group, both in the preoperative waiting area and upon returning to the ward (p < 0.01). While the quality of discharge teaching scale (QDTS) scores did not reveal a statistically significant difference between the groups (p > 0.01), the content of discharge instructions and the perceived effectiveness and skill of nurse guidance differed significantly between the control and experimental groups(p < 0.01). Notably, the experimental group experienced a demonstrably lower incidence of thirst, hunger, crying, aspiration, pain, and conversion of day ward to routine hospitalization mode compared to the control group (all p < 0.01). There was no significant difference in the incidence of postoperative nausea and vomiting between the groups after rehydration (p > 0.01)., Conclusions: The implementation of ERAS protocols enhanced by MOST within the nursing management of children with snoring undergoing day surgery demonstrates significant efficacy. This approach can effectively reduce preoperative anxiety in children, improve the quality of discharge guidance provided to parents, and demonstrably decrease the occurrence of postoperative thirst, hunger, crying, aspiration, pain, and the need for unplanned hospitalization transitions within 6 h after surgery., Relevance to Clinical Practice: It is necessary to provide fast rehabilitation nursing for children with snoring during daytime operation. Nurses should adopt the theory of fast rehabilitation based on multi-stage optimization strategy to promote children's fast rehabilitation after operation., Competing Interests: Declaration of competing interest We are hereby submitting our manuscript titled “Application of enhanced recovery after surgery based on multiphase optimization strategy in the nursing management of children with snoring disease day surgery”for consideration for publication in International Journal of Pediatric Otorhinolaryngology.All co-authors have read, approve of, and concur with the submitted manuscript. The authors believe the manuscript is a strong candidate for publication in International Journal of Pediatric Otorhinolaryngology，and have no conflicts of interest to declare. The work we describe here has not been submitted in any part for consideration for publication elsewhere and has not been previously published., (Copyright © 2024. Published by Elsevier B.V.)

Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and low-density lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPARα signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild-type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild-type and hepatic-specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPARα signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver., Competing Interests: Declaration of competing interest I, Ding Zhi Fang, declare that there are no conflicts of interest in relation to the manuscript titled " Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol " submitted to Molecular and Cellular Endocrinology. I confirm that the results and interpretations reported in the manuscript are original and have not been plagiarized. I certify that I have read and understand the Molecular and Cellular Endocrinology conflict of interest policy, and I understand that failure to disclose a conflict of interest may result in the manuscript being rejected or retracted., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate the role of volume management guided by extravascular lung water index(EVLWI) in improving the clinical outcomes and cardiac function for patients with cardiogenic shock. Methods: This study was a single-center, prospective cohort study. Patients with cardiogenic shock admitted to the Department of Cardiovascular Medicine, Shanghai East Hospital from July 2022 to December 2023 were enrolled. Patients were matched 1∶1 by propensity score and divided into EVLWI group and control group. In the control group, the volume management strategy was determined by the attending physician based mainly on conventional factors, including clinical features, biochemical assessments, and certain blood pressure measurements. In EVLWI group, the volume management plan was formulated by integrating conventional factors with EVLWI derived from pulse index continuous cardiac output (PiCCO) monitoring. Baseline clinical data, in-hospital treatment, and hemodynamic data were collected. Major adverse cardiovascular events and cardiac function related parameters were compared at 30 d after treatment between the two groups. Baseline EVLWI levels were compared between the non-survivors and the survivors in the EVLWI group. The receiver operating characteristic curve was plotted to assess the accuracy of baseline EVLWI and central venous pressure in predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, and subgroup analysis was performed according to ischemic/non-ischemic etiology and with/without use of inotropic drugs. Kaplan-Meier curve was used for survival analysis, with log-rank tests comparing all-cause mortality, cardiac death, and readmission rate for heart failure at 30 d after treatment. Results: A total of 200 patients with cardiogenic shock were enrolled, aged (71.35±12.82) years, 144(72%) males, EVLWI group and control group 100 patients each. Compared with the control group, EVLWI group had lower all-cause mortality (16%(16/100) vs. 42%(42/100), log-rank P <0.01), cardiac death (14%(14/100) vs. 34%(34/100), log-rank P <0.01), and readmission rate for heart failure (4%(4/100) vs. 12%(12/100), log-rank P =0.03) at 30 d after treatment. Subgroup analysis showed that EVLWI-guided volume management was associated with lower all-cause mortality at 30 d after treatment in patients with cardiogenic shock of ischemic or non-ischemic etiology and with or without inotropic drugs (all P <0.05). In EVLWI group, baseline EVLWI levels were higher in non-survivors than those in survivors [(15.99±6.47) ml/kg vs.(9.75±2.55) ml/kg, P <0.01]. The baseline EVLWI could predicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock, with an area under the receiver operating characteristic curve of 0.84 (95% CI : 0.75-0.94, P <0.01), while the baseline central venous pressure had no predicting value ( AUC =0.54, 95% CI : 0.40-0.69, P =0.60). The optimal cutoff value of EVLWI in pridicting all-cause mortality at 30 d after treatment in patients with cardiogenic shock was >10.3 ml/kg. With the optimization of hemodynamic parameters, left ventricular ejection fraction was improved in EVLWI group, and serum levels of N-terminal pro-brain natriuretic peptide, creatinine, alanine aminotransferase and lactic acid were decreased (all P <0.05). Conclusion: EVLWI-guided volume management exerts a beneficial effect on therapeutic decision-making and improves clinical outcomes and cardiac function in patients with cardiogenic shock.

Background: Sleep disorders are one of the major public health problems, which can potentially induce inflammation and exacerbate disease activity, resulting in compromised sleep quality. This study aimed to investigate the prevalence and risk factors associated with sleep disorders among patients with inflammatory bowel disease (IBD)., Methods: Between March 2023 and February 2024, the Pittsburgh Sleep Quality Index was employed to assess sleep quality in both IBD patients and healthy control subjects. Univariate and multivariate analysis were performed to identify the risk factors associated with SD in IBD patients., Results: Overall, 208 IBD patients [150 Crohn's disease (CD) and 58 ulcerative colitis (UC)] and 199 healthy individuals were included. Sleep disorders were observed in 59.6% of patients with IBD, with a higher prevalence among females (63.5%) compared to males (56.9%) (P = 0.476). The prevalence of sleep disorders in IBD patients was significantly higher than that found in healthy controls (37.7%) (all P < 0.01). The prevalence of sleep disorders  among CD and UC patients was 58% and 63.8%, respectively (P = 0.291). The multivariate analysis revealed that older age (OR, 1.070; 95% CI: 1.035-1.105, P = 0.000), smoking (OR, 2.698; 95% CI: 1.089-6.685, P = 0.032), and depression (OR, 4.779; 95% CI: 1.915-11.928, P = 0.001) were risk factors for sleep disorders in IBD patients. However, higher body mass index (OR, 0.879; 95% CI: 0.790-0.977, P = 0.017) was identified as a protective factor., Conclusion: Sleep disorders are common among IBD patients regardless of activity levels. Smoking and depression are the major risk factors., (© 2024. The Author(s).)

Objective: To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023. Methods: An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University's HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis. Results: A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance ( χ 2 =30.435, P <0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4 + T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P <0.05).Multivariate logistic analysis showed that the baseline CD4 + T cell count was <200/μl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P <0.05). Conclusion: The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4 + T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

Objectives: This study was to explore blood pressure levels in Chinese adolescents with different genotypes of phosphatidylethanolamine N-methyltransferase (PEMT) gene ( PEMT ) rs7946, as well as effects of dietary intake on blood pressure levels with different genders and different genotypes of PEMT rs7946., Methods: PEMT rs7946 genotypes were identified by PCR-restriction fragment length polymorphism and verified by DNA sequencing. Blood pressure was measured using a standard mercury sphygmomanometer. Dietary intakes were analyzed based on a 3-day diet diary, and dietary components were calculated using computer software., Results: A total of 721 high school students (314 males and 407 females) at the age of 16.86 ± 0.59 years were included. The A allele carriers of PEMT rs7946 had increased levels of SBP, DBP, mean arterial pressure (MAP) and pulse pressure (PP) than the GG homozygotes in the female subjects. There were significant interactions between PEMT rs7946 and gender on SBP and MAP levels, regardless of whether an unadjusted or adjusted model was used. When dietary intake was taken into account, fat intake was positively associated with SBP and PP in the male GG homozygotes, while protein intake was positively associated with PP in the female A allele carriers of PEMT rs7946., Conclusion: This study suggests that PEMT rs7946 is significantly associated with blood pressure levels in human being. There might be interactions among PEMT rs7946, gender, and dietary intake on blood pressure levels in the adolescent population., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Diabetes mellitus is generally accompanied by dyslipidaemia, but inconsistent relationships between lipid profiles and diabetes are noted. Moreover, genetic variations in insertion/deletion (I/D) polymorphisms at angiotensin-converting enzyme gene (ACE) and T/C polymorphisms in the angiotensin type 1 receptor gene (AGTR1) are related to diabetes and lipid levels, but the associations are controversial. Thus, the current research aimed to explore the effects of ACE I/D, AGTR1 rs5182 and diabetes mellitus on serum lipid profiles in 385 Chinese participants with an average age of 75.01 years., Methods: The ACE I/D variant was identified using the polymerase chain reaction (PCR) method, whereas the AGTR1 rs5182 polymorphism was identified using the PCR-based restriction fragment length polymorphism (PCR-RFLP) method and verified with DNA sequencing. Total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured using routine methods, and the lipid ratios were calculated., Results: ACE I/D, but not AGTR1 rs5182, was a predictor of TG/HDL-C for the whole study population. Both ACE I/D and AGTR1 rs5182 were predictors of HDL-C and LDL-C levels in females but not in males. Moreover, in females, diabetes mellitus and ACE I/D were identified as predictors of TG and TG/HDL-C, whereas AGTR1 rs5182 and diabetes mellitus were predictors of TG/HDL-C. Moreover, diabetes mellitus and the combination of ACE I/D and AGTR1 rs5182 variations were predictors of TG and TG/HDL-C exclusively in females., Conclusions: The results demonstrated the potential for gender-dependent interactions of ACE I/D, AGTR1 rs5182, and diabetes on lipid profiles. These findings may serve as an additional explanation for the inconsistent changes of blood lipids in individuals with diabetes mellitus, thereby offering a novel perspective for the clinical management of blood lipid levels in diabetic patients., (© 2024. The Author(s).)

Abstract: Complete remission with partial hematological recovery (CRh) has been used as an efficacy endpoint in clinical trials of nonmyelosuppressive drugs for acute myeloid leukemia (AML). We conducted a pooled analysis to characterize the clinical outcomes for patients with AML who achieved CRh after treatment with ivosidenib, olutasidenib, enasidenib, or gilteritinib monotherapy in clinical trials used to support marketing applications. The study cohort included 841 adult patients treated at the recommended drug dosage; 64.6% were red blood cell or platelet transfusion dependent at study baseline. Correlations between disease response and outcomes were assessed by logistic regression modeling for categorical variables and by Cox proportional hazards modeling for time-to-event variables. Patients with CRh had a higher proportion with transfusion independence (TI) for at least 56 days (TI-56; 92.3% vs 22.3%; P < .0001) or TI for at least 112 days (TI-112; 63.5% vs 8.7%; P < .0001), a reduced risk over time for severe infection (hazard ratio [HR], 0.43; P = .0007) or severe bleeding (HR, 0.17; P = .01), and a longer overall survival (OS; HR, 0.31; P < .0001) than patients with no response. The effects were consistent across drugs. In comparison with patients with CR, the effect sizes for CRh were similar for TI-56 and for risk over time of infection or bleeding but less for TI-112 and OS. CRh is associated with clinical benefits consistent with clinically meaningful palliative effects for the treatment of AML with nonmyelosuppressive drugs, although less robustly than for CR.

Objective: To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods: This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children's Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t -test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results: Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U =334.00, P <0.001). They were regarded as subtype "lung consolidation-atelectasis-necrosis". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype "lung consolidation-atelectasis". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions: Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as "lung consolidation-atelectasis-necrosis" and "lung consolidation-atelectasis". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.

Orphan nuclear receptors (NRs), such as COUP-TF1, COUP-TF2, EAR2, TR2 and TR4, are implicated in telomerase-negative cancers that maintain their telomeres through the alternative lengthening of telomeres (ALT) mechanism. However, how telomere association of orphan NRs is involved in ALT activation remains unclear. Here, we demonstrate that telomeric tethering of orphan NRs in human fibroblasts initiates formation of ALT-associated PML bodies (APBs) and features of ALT activity, including ALT telomere DNA synthesis, telomere sister chromatid exchange, and telomeric C-circle generation, suggesting de novo ALT induction. Overexpression of orphan NRs exacerbates ALT phenotypes in ALT cells, while their depletion limits ALT. Orphan NRs initiate ALT via the zinc finger protein 827, suggesting the involvement of chromatin structure alterations for ALT activation. Furthermore, we found that orphan NRs and deficiency of the ALT suppressor ATRX-DAXX complex operate in concert to promote ALT activation. Moreover, PML depletion by gene knockout or arsenic trioxide treatment inhibited ALT induction in fibroblasts and ALT cancer cells, suggesting that APB formation underlies the orphan NR-induced ALT activation. Importantly, arsenic trioxide administration abolished APB formation and features of ALT activity in ALT cancer cell line-derived mouse xenografts, suggesting its potential for further therapeutic development to treat ALT cancers., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objectives: The Asia Working Group of Sarcopenia (AWGS) 2019 consensus proposed a new concept named "possible sarcopenia". The present study was to estimate the association between indoor air pollution by solid fuel usages for cooking and possible sarcopenia among middle-aged and older Chinese population., Methods: A longitudinal cohort analysis was carried out using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). A total of 17,708 participants were recruited and followed up in the CHARLS. Cox proportional hazards models were used to estimate the effects of cooking fuel usages on the new onset of possible sarcopenia. Stratified analyses were performed according to gender and age, and sensitivity analyses were performed using the complete dataset., Results: A total of 4,653 participants were included in the final cohort analysis. During the follow-up of 4 years (2011-2015), a total of 1,532 (32.92%) participants developed new-onset possible sarcopenia. Compared with clean fuel usages for cooking, solid fuel usages were associated with a higher risk of possible sarcopenia (HR = 1.37, 95% CI = 1.23-1.52, p-value < 0.001). After adjusting for potential confounders, there was a trend for association between solid fuel usages and an increased risk of possible sarcopenia. Stratified analyses by gender and age demonstrated a stronger association of the solid fuel usages with possible sarcopenia in the middle-aged female participants (Model 1: HR = 1.83, 95% CI = 1.24-2.69, p-value = 0.002; Model 2: HR = 1.65, 95% CI = 1.10-2.47, p-value = 0.016). Sensitivity analyses indicated that the results were robust., Conclusion: Indoor air pollution from solid fuel usages for cooking was a modifiable risk factor for sarcopenia, especially in middle-aged female population. These findings provide a new prevention strategy to reduce the growing burden of sarcopenia, especially for middle-aged female individuals using solid fuels for cooking., Competing Interests: Conflicts of interestThe authors declare no conflicts of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024, corrected publication 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: The present study was to investigate prevalence of suicidal ideation and its associations with biological and environmental factors in adolescents with different genotypes of rs12342 at adiponectin receptor 2 gene (ADIPOR2)., Methods: Suicidal ideation, biological and environmental factors were evaluated by questionnaires in 669 high school students after Wenchuan earthquake in China. ADIPOR2 rs12342 was genotyped by polymerase chain reaction-restriction fragment length polymorphism and verified by DNA sequencing., Results: Female adolescents had higher prevalence of suicidal ideation than male students in AG heterozygote and GG homozygote, but not AA homozygote. Prevalence of suicidal ideation was different in male, but not female, subjects with different genotypes. Genotype and allele frequencies were significantly different between male students with and without suicidal ideation, but not the female counterparts. Family history of mental disorders, extent of damage to property, carbohydrate intake and protein intake were associated with suicidal ideation in female subjects, while ADIPOR2 rs12342, father's educational level and previous trauma experience were associated with suicidal ideation in male subjects., Conclusion: ADIPOR2 rs12342 is associated with and has potential to interact with environmental factors on suicidal ideation in a gender-dependent manner in youth. These findings pave a novel way and perspective for precision inferences of suicidal ideation in subjects with different genetic backgrounds. ADIPOR2 rs12342 needs to be considered when intervening suicidal ideation, especially in adolescents., (© 2024 John Wiley & Sons Australia, Ltd.)

Background and Objective: The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings. This study aims to evaluate the effectiveness and long-term efficacy of edaravone., Methods: The OVID Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched for articles published between January 1, 2000, and May 1, 2023. Two investigators independently screened the retrieved articles for randomized controlled trials (RCTs), cohort studies, or single-arm trials that evaluated the effect of edaravone on amyotrophic lateral sclerosis (ALS). The risk of bias was evaluated using the revised Cochrane Risk-of-Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk-of-Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. The primary outcome was the ALSFRS-R score assessed at month 6, with secondary outcomes including the ALSFRS-R scores evaluated at months 9, 12, and 18, forced vital capacity (FVC), and adverse events. The certainty of evidence was assessed using the GRADE approach., Results: The analysis included 16 studies with a total of 4828 participants. Among these, four were randomized controlled trials (RCTs) and 12 were observational studies. Of the RCTs, four were rated as having a low risk of bias, while six of the observational studies were rated as having a low risk of bias. Edaravone was associated with slightly slower progression in the reduction of ALSFRS-R score at month 6 compared to placebo (mean difference 1.01, 95%CI -0.87 to 3.09, p = 0.293), as shown by evidence from RCTs. However, observational studies did not show any benefit of adding edaravone to routine practice (mean difference 1.85, 95%CI -2.05 to 5.75, p = 0.352). The change from baseline in ALSFRS-R score was -2.1, -4.04, -7.5, -6.82, and -7.9 at months 3, 6, 9, 12, and 18, respectively. The GRADE assessment indicated moderate certainty for evidence from RCTs, while evidence from observational studies had very low certainty., Conclusion: Due to the limited number of studies and confounding issues in observational studies, further examination of the added benefits of edaravone to routine practice is necessary through RCTs, particularly regarding its long-term efficacy., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Objectives: To investigate the nutritional status of children with cystic fibrosis (CF) and understand the correlation between malnutrition and clinical characteristics as well as lung function., Methods: A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023. Clinical characteristics of CF children with different nutritional statuses were compared, and the correlation between malnutrition and lung function was analyzed., Results: A total of 52 CF children were included, comprising 25 boys (48%) and 27 girls (52%), aged between 7 months and 17 years. Respiratory symptoms were the predominant clinical manifestations (96%, 50/52). The prevalence of malnutrition was 65% (34/52), with moderate/severe malnutrition being the most common (65%, 22/34). The malnutrition group had a longer duration of illness, higher proportion of digestive system symptoms, and lower levels of serum albumin ( P <0.05). Pulmonary function parameters, including forced expiratory volume in one second as a percentage of the predicted value, ratio of forced expiratory volume in one second to forced vital capacity, forced expiratory flow at 25% of forced vital capacity exhaled, forced expiratory flow at 50% of forced vital capacity exhaled, forced expiratory flow at 75% of forced vital capacity exhaled, and maximum mid-expiratory flow as a percentage of the predicted value, were lower in the malnutrition group compared to the normal nutrition group ( P <0.05). Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters ( P <0.05)., Conclusions: The prevalence of malnutrition is high in CF children and is associated with decreased lung function. CF children with higher body mass index have better lung function. Therefore, screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.

Studies have shown that saikosaponin D (SSD) has favorable neurotherapeutic effects. Therefore, the objective of this study was to explore the efficacy and possible molecular mechanisms of SSD on pilocarpine (PP)-induced astrocyte injury. Primary astrocytes were isolated from juvenile rats and identified using immunofluorescence. The cells were treated with PP and/or SSD for 6 h and 12 h, respectively, followed by measurement of their viability through 3-(4,5-dimethylthiazol)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Next, quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of Glial fibrillary acidic protein (GFAP), C3, S100 calcium binding protein A10 (S100a10), pentraxin 3 (Ptx3), toll-like receptor 4 (TLR4), and RAG in astrocytes after different treatments. Enzyme-linked immunosorbent assay and biochemical tests were utilized to evaluate the level of inflammatory factors [interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)] secreted by cells and the content of oxidative stress-related factors (malondialdehyde [MDA] and glutathione [GSH]) or enzyme activity (catalase [CAT] and glutathione peroxidase [GPX]) in cells. The JC-1 mitochondrial membrane potential (MMP) fluorescence probe was used to measure the MMP in astrocytes. Additionally, western blot was applied to test the expression of proteins related to the nod-like receptor protein 3 (NLRP3)/caspase-1 signaling pathway. PP treatment (1 mM) induced cell injury by significantly reducing the viability of astrocytes and expression of cellular markers. SSD treatment (4 μM) had no toxicity to astrocytes. Besides, SSD (4 μM) treatment could significantly up-regulate the cell viability and marker expression of PP-induced astrocytes. Furthermore, SSD could be employed to inhibit inflammation (reduce IL-1β, IL-6, and TNF-α levels) and oxidative stress (decrease MDA level, elevate GSH level, the activity of CAT and GPX), and ameliorate mitochondrial dysfunction (upregulate JC-1 ratio) in PP-induced astrocytes. Moreover, further mechanism exploration revealed that SSD treatment significantly reduced the activity of the NLRP3/caspase-1 signaling pathway activated by PP induction. SSD increased cell viability, inhibited inflammation and oxidative stress response, and ameliorated mitochondrial dysfunction in PP-induced astrocyte injury model, thus playing a neuroprotective role. The mechanism of SSD may be related to the inhibition of the NLRP3/caspase-1 inflammasome., (© 2024 John Wiley & Sons Ltd.)

On October 21, 2022, the FDA approved tremelimumab (Imjudo) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma. The approval was based on the results from the HIMALAYA study, in which patients with unresectable hepatocellular carcinoma who were naïve to previous systemic treatment were randomly assigned to receive one of three study arms: tremelimumab in combination with durvalumab (n = 393), durvalumab (n = 389), or sorafenib (n = 389). The primary objective of improvement in overall survival (OS) for tremelimumab in combination with durvalumab compared with sorafenib met statistical significance with a stratified HR of 0.78 [95% confidence interval (CI), 0.66-0.92; P = 0.0035]. The median OS was 16.4 months (95% CI, 14.2-19.6) with tremelimumab in combination with durvalumab and 13.8 months (95% CI, 12.3-16.1) with sorafenib. Adverse reactions occurring in ≥20% of patients receiving tremelimumab in combination with durvalumab were rash, fatigue, diarrhea, pruritus, musculoskeletal pain, and abdominal pain. The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg, i.v., as a single dose in combination with durvalumab 1,500 mg at cycle 1/day 1, followed by durvalumab 1,500 mg, i.v., every 4 weeks. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg, i.v., as a single dose in combination with durvalumab 20 mg/kg, i.v., followed by durvalumab 20 mg/kg, i.v., every 4 weeks., (©2023 American Association for Cancer Research.)

Reactions of N,N '- bis (3-methylpyridyl)oxalamide ( L 1 ), N , N '- bis (3-methylpyridyl)adipoamide ( L 2 ) and N , N '- bis (3-methylpyridyl)sebacoamide ( L 3 ) with tricarboxylic acids and Cu(II) salts afforded {[Cu( L 1 )(1,3,5-HBTC)]·H 2 O} n (1,3,5-H 3 BTC = 1,3,5-benzenetricarboxylic acid), 1 , {[Cu 1.5 ( L 2 ) 1.5 (1,3,5-BTC)(H 2 O) 2 ]·6.5H 2 O} n , 2 , [Cu( L 2 ) 0.5 (1,3,5-HBTB)] n (1,3,5-H 3 BTB = 1,3,5-tri(4-carboxyphenyl)benzene), 3 , [Cu 4 ( L 3 )(OH) 2 (1,3,5-BTC) 2 ] n , 4 , {[Cu 3 ( L 3 ) 2 (1,3,5-BTB) 2 ]·2.5MeOH·2H 2 O} n , 5 , and {[Cu 3 ( L 3 ) 2 (1,3,5-BTB) 2 ]·DMF·2H 2 O} n , 6 , which have been structurally characterized by using single crystal X-ray crystallography. Complexes 1-4 form a 2D layer with the {4 4 .6 2 }- sql topology, a 2D layer with the (4.6 2 ) 2 (4 2 .6 2 .8 2 )- bex topology, a three-fold interpenetrated 3D net with the (4 12 ·6 3 )- pcu topology and a 3D framework with the (4 10 ·6 32 ·8 3 )(4 2 ·6) 2 (4 3 ·6 3 ) topology, respectively, whereas 5 and 6 are 3D frameworks with the (6 3 ) 2 (6 4 ·8 2 )(6 8 ·8 5 ·10 2 ) topology. Complex 5 shows a better iodine adsorption factor of 290.0 mg g -1 at 60 °C for 360 min than the other ones, revealing that the flexibility of the spacer ligand governs the structural diversity and the adsorption capacity.

On April 5, 2022, FDA granted accelerated approval to alpelisib for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy. Efficacy was evaluated using real-world data (RWD) from EPIK-P1 (NCT04285723), a single-arm clinical study in patients 2 years of age and older with severe or life-threatening PROS who received alpelisib as part of an expanded access program (EAP) for compassionate use. The primary endpoint was confirmed radiologic response rate at week 24 as determined by blinded independent central review (BICR), using volumetric-based criteria given the atypical growth pattern and irregular shape of PROS lesions. Radiologic response was defined as a ≥20% reduction from baseline in the sum of measurable target lesion volume in up to three lesions. Of the 37 patients in the efficacy population, 27% [95% confidence interval (CI), 14-44] had a radiologic response at week 24. Duration of response (DOR) was an additional efficacy outcome measure, and among responders, 60% had a response lasting ≥12 months. Furthermore, supportive clinical documentation suggested early signals of clinical benefit (i.e., improvement in PROS-related signs and symptoms). The most common (≥10%) adverse reactions were diarrhea, stomatitis, and hyperglycemia., (©2023 American Association for Cancer Research.)

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) is not only the top cause of liver diseases but also a hepatic-correlated metabolic syndrome. This study performed untargeted metabolomics analysis of NAFLD hamsters to identify the key metabolites to discriminate different stages of NAFLD., Methods: Hamsters were fed a high-fat diet (HFD) to establish the NAFLD model with different stages (six weeks named as the NAFLD1 group and twelve weeks as the NAFLD2 group, respectively). Those liver samples were analyzed by untargeted metabolomics (UM) analysis to investigate metabolic changes and metabolites to discriminate different stages of NAFLD., Results: The significant liver weight gain in NAFLD hamsters was observed, accompanied by significantly increased levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Moreover, the levels of TG, LDL-C, ALT, and AST were significantly higher in the NAFLD2 group than in the NAFLD1 group. The UM analysis also revealed the metabolic changes; 27 differently expressed metabolites were detected between the NAFLD2 and NAFLD1 groups. More importantly, the levels of N-methylalanine, allantoin, glucose, and glutamylvaline were found to be significantly different between any two groups (control, NAFLD2 and NAFLD1). Receiver operating characteristic curve (ROC) curve results also showed that these four metabolites are able to distinguish control, NAFLD1 and NAFLD2 groups., Conclusion: This study indicated that the process of NAFLD in hamsters is accompanied by different metabolite changes, and these key differently expressed metabolites may be valuable diagnostic biomarkers and responses to therapeutic interventions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an inflammatory process. Angiotensin-(1-7) may have an anti-inflammatory effect through activation of Mas receptor. This study aims to investigate whether SARS-CoV-2 SP can induce inflammation through ACE2 in the alveolar epithelial cells which can be modulated through angiotensin-(1-7)/Mas receptor axis., Methods: HPAEpiC were treated with SARS-CoV-2 SP in the presence or absence of ACE2 antagonist-dalbavancin and Mas receptor agonist-angiotensin-(1-7). Proinflammatory cytokine production (IL-6 and IL-8) were measured at mRNA and protein levels. MAP kinase phosphorylation and transcription factor activation was determined by Western Blot. Mas receptor was blocked by either antagonist (A779) or knockdown (specific SiRNA). Experiments were replicated using A549 cells., Findings: SARS-CoV-2 SP (5 μg/mL) significantly induced MAP kinase (ERK1/2) phosphorylation, downstream transcription factor (activator protein-1, AP-1) activation and cytokine production (IL-6 and IL-8) at both mRNA and protein levels. Pretreatment with dalbavancin (10 μg/mL), or angiotensin-(1-7) (10 μM) significantly reduced ERK1/2 phosphorylation, AP-1 activation, and cytokine production. However, these angiotensin-(1-7)-related protective effects were significantly abolished by blocking Mas receptor with either antagonist (A799,10 μM) or SiRNA knockdown., Interpretation: SARS-CoV-2 SP can induce proinflammatory cytokine production, which can be inhibited by either ACE2 antagonist or Mas receptor agonist-angiotensin-(1-7). Angiotensin-(1-7)-related protective effect on cytokine reduction can be abolished by blocking Mas receptor. Our findings suggest that ACE2/angiotensin-(1-7)/Mas axis may serve as a therapeutic target to control inflammatory response triggered by SARS-CoV-2 SP., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Metal clusters have become increasingly important in various applications, with ligands playing a crucial role in their construction. In this study, we synthesized a bimetallic cluster, Ag 6 Cu 8 (C=CAr) 14 (DPPB) 2 (Ag 6 Cu 8 ), using a rigid acetylene ligand, 3,5-bis(trifluoromethyl)phenylacetylide. Through single-crystal structure characterization, we discovered that the butterfly-shaped Ag 2 Cu 2 motifs were subject to distortion due to steric hindrance imposed by the rigid ligand. These motifs assembled together through shared vertices and edges. Mass spectrometry analysis revealed that the primary fragments detected during electrospray ionization (ESI) testing corresponded to the Ag 2 Cu 2 motifs. Furthermore, we conducted a comprehensive investigation of the cluster's solution properties employing 31 P NMR, UV-vis absorption, and photoluminescent measurements. In contrast to previously reported Ag/Cu bimetallic clusters protected by flexible ligands, Ag 6 Cu 8 protected by rigid ligands exhibited intriguing room temperature fluorescence properties alongside excellent thermal stability. DFT calculations on Ag 6 Cu 8 and Ag 6 Cu 8 with the rigid aromatic ring removed revealed that the presence of the rigid aromatic ring can lower the electronic energy levels of the cluster, and reduce the energy gap from 4.05 eV to 3.45 eV. Moreover, the rigid ligand further suppressed the non-radiative transition process, leading to room temperature fluorescence emission., (© 2023 Wiley-VCH GmbH.)

Structural fiber-reinforced polymer (FRP) composite materials consisting of a polymer matrix reinforced with layers of high-strength fibers are used in numerous applications, including but not limited to spacecraft, vehicles, buildings, and bridges. Researchers in the past few decades have suggested the necessary integration of sensors (e.g., fiber optic sensors) in polymer composites to enable health monitoring of composites' performance over their service lives. This work introduces an innovative cognizant composite that can self-sense, compute, and implement decisions based on sensed values. It is a critical step towards smart, resilient infrastructure. We describe a method to fabricate textile sensors with flexible circuitry and a microcontroller within the polymer composite, enabling computational operations to take place in the composite without impacting its integrity. A microstructural investigation of the sensors showed that the amount of oxidative agent and soaking time of the fabric play a major role in the adsorption of polypyrrole (PPy) on fiberglass (FG). XPS results showed that the 10 g ferric chloride solution with 6 h of soaking time had the highest degree of protonation (28%) and, therefore, higher adsorption of PPy on FG. A strain range of 30% was achieved by examining different circuitry and sensor designs for their resistance and strain resolution under mechanical loading. A microcontroller was added to the circuit and then embedded within a composite material. This composite system was tested under flexural loading to demonstrate its self-sensing, computing, and actuation capabilities. The resulting cognizant composite demonstrated the ability to read resistance values and measure strain using the embedded microcontroller and autonomously actuate an LED light when the strain exceeds a predefined limit of 2000 µε. The application of the proposed FRP system would provide in situ monitoring of structural composite components with autonomous response capabilities, as well as reduce manufacturing, production, and maintenance costs.

Radical prostatectomy (prostate removal) is a standard treatment for clinically localized prostate cancer and is often followed by postoperative radiotherapy. Postoperative radiotherapy requires accurate delineation of the clinical target volume (CTV) and lymph node drainage area (LNA) on computed tomography (CT) images. However, the CTV contour cannot be determined by the simple prostate expansion after resection of the prostate in the CT image. Constrained by this factor, the manual delineation process in postoperative radiotherapy is more time-consuming and challenging than in radical radiotherapy. In addition, CTV and LNA have no boundaries that can be distinguished by pixel values in CT images, and existing automatic segmentation models cannot get satisfactory results. Radiation oncologists generally determine CTV and LNA profiles according to clinical consensus and guidelines regarding surrounding organs at risk (OARs). In this work, we design a cascade segmentation block to explicitly establish correlations between CTV, LNA, and OARs, leveraging OARs features to guide CTV and LNA segmentation. Furthermore, inspired by the success of the self-attention mechanism and self-supervised learning, we adopt SwinTransformer as our backbone and propose a pure SwinTransformer-based segmentation network with self-supervised learning strategies. We performed extensive quantitative and qualitative evaluations of the proposed method. Compared to other competitive segmentation models, our model shows higher dice scores with minor standard deviations, and the detailed visualization results are more consistent with the ground truth. We believe this work can provide a feasible solution to this problem, making the postoperative radiotherapy process more efficient.

On January 19, 2023, the FDA granted accelerated approval to tucatinib in combination with trastuzumab for the treatment of patients with unresectable or metastatic RAS wild-type, HER2-positive colorectal cancer who have received prior treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Approval was based on the pooled analysis of patients receiving tucatinib in combination with trastuzumab in MOUNTAINEER (NCT03043313), an open-label, multicenter trial. The primary endpoint was overall response rate (ORR) by RECIST 1.1 as per blinded central review committee (BIRC) assessment. The main secondary endpoint was duration of response (DOR) per BIRC assessment. Eighty-four eligible patients received the combination tucatinib and trastuzumab. With a median follow-up of 16 months, the ORR was 38% [95% confidence interval (CI): 28-49] and median DOR was 12.4 months (95% CI: 8.5-20.5); 81% of responders had a response lasting more than 6 months. The most common adverse reactions observed in at least 20% of patients receiving tucatinib in combination with trastuzumab were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions, and fever. FDA concluded that the magnitude of ORR and durable responses observed in patients treated with tucatinib in combination with trastuzumab in the MOUNTAINEER trial are clinically meaningful, particularly in the context of a disease with estimated survival of 6-7 months with available therapy. This is the first approval for the subset of patients with HER2-positive colorectal cancer. This article summarizes the FDA's thought process and review of the data supporting this accelerated approval., (©2023 American Association for Cancer Research.)

Objective: To verify effects of rs1061622 at tumor necrosis factor-α receptor II (TNF-RII) gene (TNF-RII) on post-traumatic stress disorder (PTSD) and its interactive effects with PTSD on serum lipids levels in adolescents., Methods: PTSD was measured by PTSD Checklist-Civilian Version (PCL-C) in 699 adolescent survivors at 6 months after Wenchuan earthquake in China. A polymerase chain reaction and restriction fragment length polymorphism assay were utilized for TNF-RII rs1061622 genotyping followed by verification using DNA sequencing. Serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were tested using routine methods., Results: G (deoxyguanine) allele carriers had higher PCL-C scores than TT (deoxythymidine) homozygotes in female subjects. Female adolescents had higher PCL-C scores than male subjects in TT homozygotes. Predictors of PTSD prevalence and severity were different between G allele carriers and TT homozygotes. Subjects with PTSD had lower TG, TG/HDL-C, TC/HDL-C, and higher HDL-C than adolescents without PTSD in male G allele carriers. G allele carriers had higher TG/HDL-C and TC/HDL-C than TT homozygotes in male adolescents without PTSD, and lower TG and TG/HDL-C in male PTSD patients. G allele carriers had higher TG than TT homozygotes only in female adolescents without PTSD., Conclusion: These results suggest reciprocal actions of TNF-RII rs1061622 with other factors on PTSD severity, interplays of TNF-RII rs1061622 with PTSD on serum lipid levels, and novel treatment strategies for PTSD and comorbidities of PTSD with hyperlipidemia among adolescents with different genetic backgrounds of TNF-RII rs1061622 after experiencing traumatic events.

A comparative study of structure-property relationships in isomeric and isostructural atomically precise clusters is an ideal approach to unravel their fundamental properties. Herein, seven high-nuclearity copper(i) alkynyl clusters utilizing template-assisted strategies were synthesized. Spherical Cu 36 and Cu 56 clusters are formed with a [M@(V/PO 4 ) 6 ] (M: Cu 2+ , Na + , K + ) skeleton motif, while peanut-shaped Cu 56 clusters feature four separate PO 4 templates. Experiments and theoretical calculations suggested that the photophysical properties of these clusters are dependent on both the inner templates and outer phosphonate ligands. Phenyl and 1-naphthyl phosphate-protected clusters exhibited enhanced emission features attributed to numerous well-arranged intermolecular C-H⋯π interactions between the ligands. Moreover, the electrocatalytic CO 2 reduction properties suggested that internal PO 4 templates and external naphthyl groups could promote an increase in C 2 products (C 2 H 4 and C 2 H 5 OH). Our research provides new insight into the design and synthesis of multifunctional copper(i) clusters, and highlights the significance of atomic-level comparative studies of structure-property relationships., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Engineering of myocardial tissues has become a promising therapeutic strategy for treating myocardial infarction (MI). However, a significant challenge remains in generating clinically relevant myocardial tissues that possess native microstructural characteristics and fulfill the requirements for implantation within the human body. In this study, a thick 3D myocardial construct with anisotropic myofibers and perfusable branched vascular channels is created with clinically relevant dimensions using a customized beam-scanning stereolithography printing technique. To obtain tissue-specific matrix niches, a decellularized extracellular matrix microfiber-reinforced gelatin-based bioink is developed. The bioink plays a crucial role in facilitating the precise manufacturing of a hierarchical microstructure, enabling us to better replicate the physiological characteristics of the native myocardial tissue matrix in terms of structure, biomechanics, and bioactivity. Through the integration of the tailored bioink with our printing method, we demonstrate a biomimetic architecture, appropriate biomechanical properties, vascularization, and improved functionality of induced pluripotent stem cell-derived cardiomyocytes in the thick tissue construct in vitro. This work not only offers a novel and effective means to generate biomimetic heart tissue in vitro for the treatment of MI, but also introduces a potential methodology for creating clinically relevant tissue products to aid in other complex tissue/organ regeneration and disease model applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lijie Grace Zhang reports financial support was provided by American Heart Association. Lijie Grace Zhang reports financial support was provided by National Science Foundation. Lijie Grace Zhang has patent pending to The George Washington University., (Copyright © 2023. Published by Elsevier B.V.)

We compute for the first time the long-distance penguin contribution to the double radiative B-meson decays by applying the perturbative factorization theorem. The numerically dominant penguin amplitude arises from the soft-gluon radiation off the light up-quark loop rather than the counterpart charm-loop effect. Importantly, the long-distance up-quark penguin contribution brings about the substantial cancellation of the known factorizable power correction, thus enabling B&#95;{d,s}→γγ to become new benchmark probes of physics beyond the standard model.

Temporal coherence and spectral regularity are critical cues for human auditory streaming processes and are considered in many sound separation models. Some examples include the Conv-tasnet model, which focuses on temporal coherence using short length kernels to analyze sound, and the dual-path convolution recurrent network (DPCRN) model, which uses two recurring neural networks to analyze general patterns along the temporal and spectral dimensions on a spectrogram. By expanding DPCRN, a harmonic-aware tri-path convolution recurrent network model via the addition of an inter-band RNN is proposed. Evaluation results on public datasets show that this addition can further boost the separation performances of DPCRN., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Metal-directed interfacial self-assembly of well-defined coordination polymer (CP) ultrathin films can control the metal complex arrangement and distribution at the molecular level, providing a convenient route for the design and fabrication of novel opto-electrical devices and heterogeneous catalysts. Here, we report the assembly of two series of CP multilayers with the transition-metal ions of Fe 2+ , Co 2+ , Zn 2+ and Tb 3+ as connectors and tripodal terpyridyl ligands of 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-(4-([2,2':6',2″-terpyridin]-4'-yl)benzyl)pyridin-1-ium) (TerPyTa) and 4,4',4″-(benzene-1,3,5-triyl)tris(1-(4-([2,2':6',2″-terpyridin]-4'-yl)benzyl)pyridin-1-ium) (TerPyBen) as linkers at the air-water interface. The as-prepared Langmuir-Blodgett (LB) films display strong luminescence, with the emission wavelength and relative intensity dependent on both the metal ions and linkers; among them, the Zn-TerPyTa and Zn-TerPyBen CPs give off the strongest luminescent emission centered at about 370 nm with an emission lifetime of approximately 0.2-0.3 ns. The Tb-TerPyTa CPs can give off emission at approximately 490, 546, 586, and 622 nm, attributed to the 5 D 4 to 7 F 3-6 electron transitions of typical Tb 3+ ions. Finally, these CP LB films can act as efficient heterogeneous photocatalysts for the CO 2 reduction to selectively produce CO. The catalytic efficiency can be optimized by adjusting the experimental conditions (light sensitizer, electron donor, and water content) and CP composition (metal ion and ligand) with an excellent yield of up to 248.1 mmol g -1 . In particular, it is revealed that, under the same conditions, the catalytic efficiency of the Fe-TerPyTa CP LB film is nearly 2 to 3 orders of magnitude higher than that of the other metalated complexes investigated in the homogeneous system. UV-vis spectroscopy and cyclic voltammetry studies demonstrated that the dual active sites of Fe-terpyridine and TerPyTa units contribute to the enhanced catalytic activity. This work provides an effective method to introduce the earth-abundant metal complexes into CP films to construct efficient noble-metal-free photocatalysts for the CO 2 reduction.

The harvest period of cultivated ginseng is generally 4-6 years. Ginseng flowers (GFs), the nonmedicinal parts, are usually removed every autumn, in which components are generally believed to stay unchanged with the increasing cultivation age. Recently, few documents were reported on the variation of volatile organic compounds (VOCs) and other components about ginseng flowers. This study had an insight into the variation of the chemical constituents with the cultivation ages through the comparison of the volatile organic compounds, gross ginsenosides, crude polysaccharide, and gross proteins of ginseng flowers from 3-, 4-, 5-, and 6-yr-old (GF3, GF4, GF5, and GF6) which were conducted by headspace solid-phase microextraction-gas chromatography-triple quadrupole mass spectrometry (HS-SPME-GC-QQQ/MS) and spectroscopic analysis combined with multivariate statistical analysis, including one-way ANOVA analysis and T test. The results indicated that the crude polysaccharide contents raised significantly depending on cultivation age except 6-yr-old, whereas the gross ginsenosides and the gross protein content were indistinctive. According to the peak intensity of determined VOCs, the contents of most differential compounds arranged in an order from high to low are GF3, GF4, GF5, and GF6, such as the compounds 2 - 15 , 17 - 19 , 22 , and 25 - 26 , therefore, they can be inferred that they are important markers to identify the age of GFs. 461 common differential compounds were gained and 26 common volatile organic compounds were identified with RSI >800 and RI and RIx no more than 30, including alcohols (such as 11 , 12 , and 15 ), sesquiterpenes (such as 2 , 3 , and 4 ), esters (such as 1 and 26 ), naphthalene and naphthol (such as 7 and 20 ), which had potential effects on curing Alzheimer's disease, inflammatory diseases, and prostate cancer based on network pharmacology analysis. This paper firstly revealed the variation rules of constitutions of GFs, which may provide a reference for the harvest and making rational application., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Lian-Yun Du et al.)